Conjugates of TAT and folate with DOX-loaded chitosan micelles offer effective intracellular delivery ability.

The key for better antitumor efficacy is to improve the specificity of antitumor drugs for tumor cells and diminish their cytotoxicity to normal tissues. Targeted nanoparticles as antitumor drug delivery system can resolve this problem. In this study, we prepared folate and TAT (arginine-rich cell-penetrating peptide) modified N-PEG-N'-octyl-chitosan to form the folate/TAT-PEG-OC micelles. Then, the molecular structure, morphology, size distribution and bio-safety of the micelles were characterized. In order to investigate the drug-loading capacity of folate/TAT-PEG-OC micelles, doxorubicin (DOX) was used as model drug to prepare DOX-loaded chitosan micelles. Here, the confocal microscopy was used to evaluate the cellular uptake of DOX/folate/TAT-PEG-OC micelles, while the self-built NIR imaging system was used to evaluate the dynamic behavior of ICG-Der-01/folate/TAT-PEG-OC micelles in vivo. Our results demonstrate that the dual-modified PEG-OC micelles not only have good morphology, uniform size distribution and excellent drug loading capacity, but also show a strong capability for the efficient intracellular uptake and enhanced targeting behaviors in a folate receptor positive tumor model (Bel-7402 human hepatocellular cells). All these results suggest the potential application of folate/TAT-PEG-OC micelles in the targeted diagnosis and therapy to different kinds of folate receptor positive tumors.